Consilium MedicumConsilium MedicumConsilium MedicumConsilium Medicum2075-17532542-2170Consilium Medicum9489510.26442/2075-1753_19.10.60-65ArticlesСтатьиReview ArticleThe evolution of mineralocorticoid receptor antagonists: spironolactone and eplerenoneЭволюция антагонистов минералокортикоидных рецепторов: эплеренон и спиронолактонLeonovaM. V.ЛеоноваМарина Васильевна

д-р мед. наук, проф., зав. каф. клин. фармакологии лечебного фак-та

anti23@mail.ruAlimovaE. EАлимоваЭльмира Эрфановна

канд. мед. наук, доц. каф. клин. фармакологии лечебного фак-та

EreminaYu. NЕреминаЮлия Николаевна

канд. мед. наук, доц. каф. клин. фармакологии лечебного фак-та

N. I.Pirogov Russian National Research Medical University of the Ministry of Health of the Russian FederationФГБОУ ВО «Российский национальный исследовательский медицинский университет им. Н.И.Пирогова» Минздрава России151020171910VOL 19, NO10 (2017)ТОМ 19, №10 (2017)606528122021Copyright ©; 2017, Consilium MedicumCopyright ©; 2017, ООО "Консилиум Медикум"2017Consilium MedicumООО "Консилиум Медикум"https://creativecommons.org/licenses/by-nc-sa/4.0https://consilium.orscience.ru/2075-1753/article/view/94895

This article presents the overview of the scientific data and the results of clinical studies of mineralocorticoid receptor antagonists. Spironolactone is a selective mineralocorticoid receptor antagonist and has affinity for androgen and progesterone receptors, whereas eplerenone - is a highly selective antagonist. Differences in the pharmacokinetics of drugs are metabolism and the relationship between the drug and plasma proteins: eplerenone is not unexposed to presystemic metabolism and has relatively low (approximately 50%) level of plasma proteins. We have many evidence-based clinical studies concerning eplerenone in the treatment of arterial hypertension in both monotherapy and in combination with other drugs; high effectiveness of antihypertensive effect in comparison with other drugs. Eplerenone shows organ-protective effect on the regression of left ventricular hypertrophy and microalbuminuria (4E-LVH-Study). The efficiency of eplerenone is described in the treatment of patients with chronic heart failure (EPHESUS, EMPHASIS-HF). Eplerenone has good tolerance and lower frequency of side effects in the sexual sphere.

В статье представлены обзор научных данных и результаты клинических исследований антагонистов минералокортикоидных рецепторов. Спиронолактон - неселективный антагонист минералокортикоидных рецепторов, имеет аффинность к андрогенными и прогестероновым рецепторам, тогда как эплеренон - высокоселективный антагонист. Различиями в фармакокинетике препаратов являются метаболизм и связь с белками плазмы: эплеренон не подвержен пресистемному метаболизму и имеет относительно невысокую (около 50%) степень связи с белками плазмы. Имеется большая доказательная база клинических исследований эплеренона в лечении артериальной гипертензии как в монотерапии, так и в комбинации с другими препаратами; показана его высокая антигипертензивная эффективность в сравнении с другими препаратами. Эплеренон показал органопротективные эффекты по регрессу гипертрофии левого желудочка и микроальбуминурии (4E-LVH-Study). Эффективность эплеренона показана в лечении пациентов с хронической сердечной недостаточностью (EPHESUS, EMPHASIS-HF). Эплеренон имеет хорошую переносимость и меньшую частоту побочных эффектов в половой сфере.

mineralocorticoid receptor antagonistseplerenonearterial hypertensiontarget organsheart failureантагонисты минералокортикоидных рецепторовэплеренонартериальная гипертензияорганы-мишенисердечная недостаточностьGarthwaite S.M, McMahon E.G. The evolution of aldosterone antagonists. Mol Cell Endocrinol 2004;217:27-31.Mihailidou A.S, Funder J.W. Nongenomic effects of mineralocorticoid receptor activation in the cardiovascular system. Steroids 2005; 70 (5-7): 347-51.Sica D.A. Pharmacokinetics and pharmacodynamics of mineralocorticoid blocking agents and their effects on potassium homeostasis. Heart Failure Reviews 2005; 10: 23-9.Pitt B, Gheorghiade M, Zannad F. et al. Evaluation of eplerenone in the subgroup of EPHESUS patients with baseline left ventricular ejections fraction №30%, Eur J Heart Fail 2006;8:295-301.Seferovic P.M, Pelliccia F, Zivkovic I et al. Review mineralocorticoid receptor antagonists, a class beyond spironolactone - focus on the special pharmacologic properties of eplerenone. Int J Cardiol 2015; 200: 3-7.Williams B, MacDonald T.M, Morant S et al. Spironolactone versus placebo, bisoprolol, and doxazosin to determine the optimal treatment for drug-resistant hypertension (PATHWAY-2): a randomised, double-blind, crossover trial. Lancet 2015; 386: 2059-68.2013 ESH/ESC Guidelines for the management of arterial hypertension. The Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Eur Heart J 2013; 34: 2159-219.Weinberger M.H, Roniker B, Krause S.L, Weiss R.J. Eplerenone, a selective aldosterone blocker, in mild-to-moderate hypertension. Am J Hypertens 2002; 15: 709-16.White W.B, Carr A.A, Krause S. et al. Assessment of the novel selective aldosterone blocker eplerenone using ambulatory and clinical blood pressure in patients with systemic hypertension. Am J Cardiol 2003; 92: 38-42.Williams G.H, Burgess E, Kolloch R.E et al. Efficacy of eplerenone versus enalapril as monotherapy in systemic hypertension. Am J Cardiol 2004; 93 (8): 990-6.White W.B, Duprez D, St Hillaire R. et al. Effects of the selective aldosterone blocker eplerenone versus the calcium antagonist amlodipine in systolic hypertension. Hypertension 2003;41:1021-6.Flack J.M, Oparil S, Pratt J.H. et al. Efficacy and tolerability of eplerenone and losartan in hypertensive black and white patients. J Am Coll Cardiol 2003; 41: 1148-55.Pelliccia F, Patti G, Rosano G. et al. Efficacy and safety of eplerenone in the management of mild to moderate arterial hypertension: systematic review and meta-analysis. Int J Cardiol 2014; 177 (1): 219-28.Epstein M. Aldosterone receptor blockade and the role of eplerenone: evolving perspectives. Nephrol Dial Transplant 2003; 18: 1984-92.Pitt B, Reichek N, Willenbrock R. et al. Effects of eplerenone, enalapril, and eplerenone/enalapril in patients with essential hypertension and left ventricular hypertrophy: the 4E-left ventricular hypertrophy study. Circulation 2003; 108: 1831-8.Epstein M, Williams G.H, Weinberger M et al. Selective Aldosterone Blockade with Eplerenone Reduces Albuminuria in Patients with Type 2 Diabetes. Clin J Am Soc Nephrol 2006; 1:940-51.Pitt B, Zannad F, Remme W.J et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. N Engl J Med 1999; 341: 709-17.Chen Y, Wang H, Lu Y. et al. Effects of mineralocorticoid receptor antagonists in patients with preserved ejection fraction: a meta-analysis of randomized clinical trials. BMC Medicine 2015;13:10.Bapoje S.R, Bahia A, Hokanson J.E et al. The Effects of Mineralocorticoid Receptor Antagonists on the Risk of Sudden Cardiac Death in Patients with Left Ventricular Systolic Dysfunction: A Meta-analysis of Randomized Controlled Trials. Circ Heart Fail 2013; 2.2016 E.S.C Guidelines for the diagnosis and treatment of acute and chronic heart failure. The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J 2016.Pitt B, Remme W, Zannad F et al. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med 2003; 348: 1309-21.Zannad F, McMurray J.J.V, Krum H. et al. Eplerenone in patients with systolic heart failure and mild symptoms. N Engl J Med 2011; 364 (1): 11-21.Danjuma M.I, Mukherjee I, Makaronidis J, Osula S. Converging Indications of Aldosterone Antagonists (Spironolactone and Eplerenone): A Narrative Review of Safety Profiles. Curr Hypertens Rep 2014; 16: 414.Burgess E, Lacourciere Y, Ruilope L.M et al. Assessment of the long-term safety and efficacy of the selective aldosterone blocker eplerenone in patients with essential hypertension. Clin Ther 2003; 25: 2388-404.